Risk of Pneumonia Associated with Inhaled Corticosteroid in Patients with Chronic Obstructive Pulmonary Disease: A Korean Population-Based Study

Figures & data

Figure 1 Patient selection flowchart.

Table 1 Baseline Characteristics of the Study Subjects

	ICS Users (n=22,161)		Non-ICS Users (n=22,161)		P value
	n	%	n	%
Age
Mean (SD)	65.4 (11.0)		65.4 (11.0)		0.9281
40–49	1968	8.88	2021	9.12	0.4082
50–59	4590	20.71	4742	21.40
60–69	7106	32.07	7059	31.85
70–79	6329	28.56	6208	28.01
≥ 80	2168	9.78	2131	9.62
Sex
Male	16,044	72.40	15,935	71.91	0.2435
Female	6117	27.60	6226	28.09
Comorbidity
Asthma	10,926	49.30	11,318	51.07	0.0060
Interstitial lung disease	325	1.47	344	1.55	0.3115
Diabetes	5623	25.37	5665	25.56	0.5779
Hypertension	10,105	45.60	10,242	46.22	0.0859
Heart failure	3746	16.90	3792	17.11	0.5436
Chronic kidney disease	839	3.79	881	3.98	0.3247
Chronic liver disease	6609	29.82	6716	30.31	0.1557
CCI
Mean (SD)	2.78 (1.94)		2.83 (1.98)		0.0375
< 2	12,195	55.03	0.0050	53.96	0.0050
≥ 2	9966	44.97	10,203	46.04
Bronchodilator
SABA	1261	5.69	6166	27.82	<0.0001
LAMA	119	0.54	8761	39.53
LABA	15,054	67.93	1037	4.68
LAMA + LABA	5727	25.84	6197	27.96
Severe exacerbation of COPD
Yes	990	4.47	1045	4.72	0.1880
No	21,171	95.53	16,729	95.28
OCS prescription
Yes	17,186	77.55	17,322	78.16	0.1336
No	4975	22.45	4839	21.84
OCS prescription day
Mean (SD)	8.44 (13.56)		7.79 (13.93)		<0.0001
Interval from COPD diagnosis to index date
Mean (SD)	315.3 (711.7)		344.6 (801.5)		<0.0001

Abbreviations: ICS, inhaled corticosteroid; LAMA, long-acting muscarinic antagonist; LABA, long-acting β₂ agonist.

Table 2 Characteristics of Inhaled Corticosteroid Users

	ICS User (Total 22,261)
	n	%
ICS cumulative dose
Mean (SD)	132,315.7 (338,241.0)
Medium (Q1, Q3)	30,720 (15,000, 107,160)
1–15,000 μg	5542	25.01
15,001–30,720 μg	5925	26.73
30,721–107,160 μg	5156	23.27
> 107,610 μg	5538	24.99
ICS dose
Low	13,477	60.81
Medium	7330	33.08
High	1354	6.11
Type of ICS
Fluticasone propionate	11,436	51.60
Budesonide	5062	22.80
Beclomethasone	2156	9.73
Ciclesonide	997	4.50
Fluticasone furoate	2520	11.37

Abbreviation: ICS, inhaled corticosteroid.

Table 3 Crude Incidence Rate of Pneumonia According to the ICS Type and Dose

Variables	Person Year	Pneumonia Patients	Incidence Rate (per 100,000)
Non-ICS user	87,517.00	5432	6206.79
ICS user	83,919.32	7473	8904.98
ICS cumulative dose (μg)
1–15,000	22,396.12	1659	7407.53
15,000–30,720	18,486.25	1387	7502.87
30,721–107,160	20,264.26	1900	9376.11
> 107,610	22,772.68	2527	11,096.63
ICS dose
Low	48,189.90	4227	8771.55
Medium	30,602.72	2793	9126.64
High	5126.70	453	8836.10
Type of ICS
Fluticasone propionate	49,698.20	4689	9434.95
Budesonide	21,076.88	1605	7614.98
Beclomethasone	6139.31	515	8388.57
Ciclesonide	3902.04	283	7252.61
Fluticasone furoate	3102.88	381	12,278.90

Abbreviation: ICS, inhaled corticosteroid.

Figure 2 Survival analysis of the development of pneumonia using Kaplan–Meier curve according to the use of inhaled corticosteroid (ICS) (A), cumulative dose of ICS (B), and daily dose of ICS (C).

Figure 3 Hazard ratios of pneumonia according to the use of inhaled corticosteroid (ICS) and subtype of ICS users.